The bis(2,6-dioxopiperazine), ICRF-193, is potent non-DNA damaging inhibitor of the decantenation activity of topoisomerase II. The mechanism of inhibition is being interpreted in terms of an ATP-modulated protein-clamp model. ICRF-193 inhibits cell division but allows cell cycle traverse and progression to polyploidy with a delay at the G2 checkpoint. We will use conventional FCM methods to examine cell cycle regulation in conjunction with the various cyclins, including A and B1 and fluorescence lifetime analysis will be performed on cellular-bound ICRF-123 to analyze its interaction with chromatin.